Protein synthesis is required for consolidation of memory and has been used to characterize memory systems. However, it is not clear whether protein synthesis can regulate synaptic plasticity at the level of single synapses and how protein synthesis affects synaptic structures, such as dendritic spines. Tanaka et al. (see the Perspective by Korte) discovered that repetitive synaptic stimulation in synchrony with postsynaptic spike induces rapid and long-term spine enlargement, which occurs at the level of single spines and is associated with increases in glutamate sensitivity. This associative paradigm specifically produces long-term and protein synthesis-dependent changes. Brain-derived neurotrophic factor (BDNF) mimics the effects of postsynaptic spiking and occludes the effects of associative stimulation. Thus, protein synthesis and BDNF are required for the alterations in spine morphology associated with synaptic plasticity.